Ponesimod
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Also known as ACT-128800Ponvory
Summary
Ponesimod (CHEMBL1096146) is an approved small molecule (ATC L04AE04) targeting S1PR1, S1PR3, and S1PR4; indicated across 4 conditions including multiple sclerosis and relapsing-remitting multiple sclerosis.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: L04AE04
- Targets: 4 (S1PR1, S1PR3, S1PR4…)
- Indications: 4 conditions
- Clinical trials: 17
- Chemistry: 461 Da · C23H25ClN2O4S
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL1096146 |
| Name | Ponesimod |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | no |
| PubChem CID | 11363176 |
| ATC | L04AE04 |
| Molecular formula | C23H25ClN2O4S |
| Molecular weight | 461 |
| InChIKey | LPAUOXUZGSBGDU-ULCCENQXSA-N |
SMILES: CCCN=C1N(C(=O)/C(=C/C2=CC(=C(C=C2)OC[C@@H](CO)O)Cl)/S1)C3=CC=CC=C3C
IUPAC name: (5Z)-5-[[3-chloro-4-[(2R)-2,3-dihydroxypropoxy]phenyl]methylidene]-3-(2-methylphenyl)-2-propylimino-1,3-thiazolidin-4-one
Also known as: ACT-128800, Ponesimod, Ponvory, PONESIMOD
Patent coverage: 268 distinct patent families (672 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 623 (93%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| S1PR1 | S1P1 receptor | Agonist | 8.04 | 0.2% | P21453 |
| S1PR3 | S1P3 receptor | Agonist | 5.68 | 0.2% | Q99500 |
| S1PR4 | S1P4 receptor | Partial agonist | 5.71 | 0.2% | O95977 |
| S1PR5 | S1P5 receptor | Partial agonist | 6.85 | 0% | Q9H228 |
Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Sphingosine 1-phosphate receptor 3, Sphingosine 1-phosphate receptor 1.
Bioactivity
ChEMBL activities: 4 potent at pChembl ≥ 5 of 4 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| S1PR1 | 8.01 | EC50 | 9.7 | nM | CHEMBL_ACT_3290999 |
| S1PR1 | 8 | EC50 | 10 | nM | CHEMBL_ACT_25708619 |
| S1PR1 | 7.9 | IC50 | 12.59 | nM | CHEMBL_ACT_18763125 |
| S1PR3 | 6.96 | EC50 | 109 | nM | CHEMBL_ACT_3290930 |
Target pathways
Aggregated over 4 target gene(s): S1PR1, S1PR3, S1PR4, S1PR5.
Top Reactome pathways
19 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Signal Transduction | 4 | S1PR1, S1PR3, S1PR4, S1PR5 |
| Signaling by GPCR | 4 | S1PR1, S1PR3, S1PR4, S1PR5 |
| Class A/1 (Rhodopsin-like receptors) | 4 | S1PR1, S1PR3, S1PR4, S1PR5 |
| Lysosphingolipid and LPA receptors | 4 | S1PR1, S1PR3, S1PR4, S1PR5 |
| GPCR ligand binding | 4 | S1PR1, S1PR3, S1PR4, S1PR5 |
| GPCR downstream signalling | 3 | S1PR3, S1PR4, S1PR5 |
| G alpha (i) signalling events | 3 | S1PR3, S1PR4, S1PR5 |
| Cytokine Signaling in Immune system | 1 | S1PR1 |
| Disease | 1 | S1PR1 |
| Immune System | 1 | S1PR1 |
| Signaling by Interleukins | 1 | S1PR1 |
| Infectious disease | 1 | S1PR1 |
| Interleukin-4 and Interleukin-13 signaling | 1 | S1PR1 |
| ESR-mediated signaling | 1 | S1PR3 |
| Signaling by Nuclear Receptors | 1 | S1PR3 |
| Extra-nuclear estrogen signaling | 1 | S1PR3 |
| Potential therapeutics for SARS | 1 | S1PR1 |
| SARS-CoV Infections | 1 | S1PR1 |
| Viral Infection Pathways | 1 | S1PR1 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| sphingosine-1-phosphate receptor signaling pathway | 4 |
| G protein-coupled receptor signaling pathway | 4 |
| adenylate cyclase-activating G protein-coupled receptor signaling pathway | 4 |
| signal transduction | 4 |
| adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | 2 |
| positive regulation of cell population proliferation | 2 |
| angiogenesis | 1 |
| blood vessel maturation | 1 |
| cardiac muscle tissue growth involved in heart morphogenesis | 1 |
| chemotaxis | 1 |
| cell adhesion | 1 |
| phospholipase C-activating G protein-coupled receptor signaling pathway | 1 |
| brain development | 1 |
| cell population proliferation | 1 |
| cell migration | 1 |
Indications & clinical
Indications
4 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| multiple sclerosis | 4 | MONDO:0005301 | MONDO:0005301 |
| relapsing-remitting multiple sclerosis | 4 | MONDO:0005314 | EFO:0003929 |
| psoriasis | 2 | MONDO:0005083 | EFO:0000676 |
1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 17.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE1 | 6 |
| PHASE3 | 4 |
| PHASE2 | 4 |
| Not specified | 3 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT07362017 | PHASE3 | NOT_YET_RECRUITING | Open Label Study to Investigate the Safety and Efficacy of Ponesimod in Moderate-to-Severe Chronic Plaque Psoriasis |
| NCT02425644 | PHASE3 | COMPLETED | Oral Ponesimod Versus Teriflunomide In Relapsing MUltiple Sclerosis |
| NCT02907177 | PHASE3 | TERMINATED | Clinical Study to Compare the Efficacy and Safety of Ponesimod to Placebo in Subjects With Active Relapsing Multiple Sclerosis Who Are Treated With Dimethyl Fumarate (Tecfidera®) |
| NCT03232073 | PHASE3 | COMPLETED | Long-term Extension to Study AC-058B301 to Investigate Safety, Tolerability and Disease Control of Ponesimod 20 mg in Patients With Relapsing Multiple Sclerosis |
| NCT00852670 | PHASE2 | COMPLETED | ACT-128800 in Psoriasis |
| NCT01093326 | PHASE2 | COMPLETED | Clinical Study to Investigate the Long-term Safety, Tolerability, and Efficacy of Ponesimod in Patients With Relapsing-remitting Multiple Sclerosis |
| NCT01208090 | PHASE2 | COMPLETED | ACT-128800 in Patients With Moderate to Severe Chronic Plaque Psoriasis |
| NCT02461134 | PHASE2 | TERMINATED | Clinical Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of Ponesimod in Subjects With Symptomatic Chronic GVHD |
| NCT02029482 | PHASE1 | COMPLETED | Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-128800 in Healthy Subjects |
| NCT02068235 | PHASE1 | COMPLETED | Study to Investigate the Absolute Bioavailability of a Single Oral Dose of Ponesimod in Healthy Male Subjects |
| NCT02126956 | PHASE1 | COMPLETED | Mass Balance, Pharmacokinetics, and Metabolism of 14C-labeled ACT-128800 Administered to Healthy Male Subjects |
| NCT02136888 | PHASE1 | COMPLETED | Study of the Electrocardiographic Effects of Ponesimod in Healthy Male and Female Subjects |
| NCT02223832 | PHASE1 | COMPLETED | Study to Evaluate the Pharmacokinetics, Tolerability, and Safety of ACT-128800 in Japanese and Caucasian Healthy Male and Female Subjects |
| NCT05552196 | PHASE1 | COMPLETED | A Study of Ponesimod in Healthy Adult Participants |
| NCT03500328 | Not specified | ACTIVE_NOT_RECRUITING | Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial |
| NCT05688436 | Not specified | RECRUITING | A Study to Learn More About The Safety of Diroximel Fumarate (VUMERITY®) in Participants Who Took it During Pregnancy And About the Health of Their Babies |
| NCT05762003 | Not specified | COMPLETED | Czech Pharmaco-epidemiological Study on Disease Modifying Drugs |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
10 molecules share ≥1 primary target. Top 10 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| FINGOLIMOD | ChEMBL + PubChem | Phase 4 (approved) | S1PR1, S1PR3, S1PR4, S1PR5 |
| OZANIMOD | ChEMBL + PubChem | Phase 4 (approved) | S1PR1, S1PR3, S1PR4, S1PR5 |
| SIPONIMOD | ChEMBL + PubChem | Phase 4 (approved) | S1PR1, S1PR3, S1PR4, S1PR5 |
| ETRASIMOD | ChEMBL + PubChem | Phase 4 (approved) | S1PR1, S1PR4, S1PR5 |
| CENERIMOD | ChEMBL | Phase 3 | S1PR1 |
| AMISELIMOD | ChEMBL | Phase 2 | S1PR1 |
| ICANBELIMOD | ChEMBL | Phase 2 | S1PR1 |
| NIGULDIPINE | ChEMBL | Phase 2 | S1PR1 |
| PINAFIDE | ChEMBL | Phase 2 | S1PR1 |
| Belzutifan | PubChem | Approved | S1PR3 |
Related Atlas pages
- Genes: S1PR1, S1PR3, S1PR4, S1PR5
- Diseases: multiple sclerosis, relapsing-remitting multiple sclerosis
- Drugs: Fingolimod, Ozanimod, Siponimod, Etrasimod, Cenerimod, Belzutifan